Positron emission tomography (PET) is a non-invasive technique that allows serial metabolic measurements to be obtained in a single subject. PET imaging is particularly useful in assessing myocardial viability via the ability of this technique to demonstrate metabolic consequences of myocardial ischemia. Using PET imaging, myocardial segments that are likely to improve after revascularization can be identified. Further, this technique can be used in the detection of coronary artery disease and serves as an alternative test for patients who cannot undergo treadmill exercise stress testing.
Adenosine is administered routinely as a pharmacologic stress agent to assess cardiac disease by positron emission tomography. For this assessment, a separate radiolabeled tracer is also administered to the patient. Adenosine is preferred as a vasodilator over dipyramidole as it produces maximum vasodilation in a significantly greater percentage of patients and is a more potent coronary vasodilator (Gupta et al. Am. Heart J. 122:293-301 (1991)). Further, adenosine's short half-life is ideal for use with the very short half-life radiotracers used for PET.
A number of radiotracers or imaging agents have been described for use in PET in conjunction with adenosine. Some examples include 13N-ammonia (Beanlands et al. J. Nucl. Cardiol. 1(3):225-35 (1994); Gewirtz et al. Cardiology, 88(1):62-70 (1997)), 2-[18F]fluoro-2-deoxy-D-glucose (McFalls et al. 272:343-9 (1997)), and 15O2 (Yamamoto et al. Circulation, 94(4):808-16 (1996)). Thallium-201- and technetium-labeled perfusion agents are also used in accessing myocardial perfusion (Iskandrian et al. J. Nucl. Cardiol., 1(1):94-111 (1994)). In addition, 11C methyl triphenyl phosphonium has been disclosed as a promising PET agent for cardiac imaging. The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A1 adenosine receptor has also been suggested to provide good leads for developing radioligands suitable for PET (Holsbach et al., J. Med. Chem., 41(4):555-63 (1998)).
Radiofluorinated ethyluracil and deoxyadenosine analogues have also been used in the noninvasive assessment of tumor proliferation by PET (Kim et al., J. Pharm. Sci., 85(3):339-44 (1996)).
Attempts have been made to study adenylate metabolism but these methods are limited to rapid hydrolysis that occurs with rapid loss of label. Additionally, existing methods for biological imaging have limitations including undesirable sensitivities and decreased specificity of existing imaging agents. Other problems include inability to cross the blood brain barrier and difficulties with localization. Therefore, a need exists for developing new PET imaging agents with improved properties.